Asymmetric heterocyclic ester derivatives of 1,4-dihydropyridine-3,5-dicarboxylic acids

Abstract

The present invention relates to new asymmetric heterocyclic ester derivatives of 1,4-dihydropyridine-3,5-dicarboxylic acids of the formula: ##STR1## wherein R 1 is a C 1 -C 4 -alkyl group; X and Y, which are identical or different, each represent O or S, at least one of the symbols X and Y being different from S; n is an integer equal to 1 or 2; and R 2 and R 3 , which are identical or different, each represent H, CH 3 , CF 3 , C 6 H 5 or halogenophenyl, it being possible for R 2 and R 3 , taken together, to form a 5-membered to 7-membered spirocycloaliphatic group with the C atom of the heterocyclic group to which they are bonded; and their optical iomers and diastereoisomers. These new derivatives are useful as pharmaceuticals, in particular as vasodilators.

What is claimed is: 
     
       1. An asymmetric heterocyclic ester compound of a 1,4-dihydropyridine-3,5-dicarboxylic acid, selected from the group consisting of: (i) 1,4-dihydro-2,6-dimethylpyridine-3,5-dicarboxylic acid esters of the formula: ##STR46##  wherein R 1  is a C 1  -C 4  -alkyl group; X and Y, which are identical or different, each represent O or S, at least one of the symbols X and Y being different from S; n is an integer equal to 1 or 2; and R 2  and R 3 , which are identical or different, each represent the hydrogen atom, the methyl group, the trifluoromethyl group, the phenyl group or a halogenophenyl group, wherein R 2  and R 3  taken together, can form a 5-membered to 7-membered spirocycloalkyl group with the carbon atom of the heterocycle to which they are bonded;   (ii) optical isomers thereof; and   (iii) diastereoisomers thereof.   
     
     
       2. A compound according to claim 1, wherein R 2  and R 3  form a cyclopentyl, cyclohexyl or cycloheptyl radical with the carbon atom of the heterocyclic group to which they are bonded. 
     
     
       3. A compound according to claim 1, wherein R 2  and R 3 , which are identical or different, each represent H, CH 3 , CF 3 , C 6  H 5  or 2,4-dichlorophenyl. 
     
     
       4. A compound according to claim 1, which is methyl (2,2-dimethyl-1,3-dioxolan-4-yl)methyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)pyridine-3,5-dicarboxylate. 
     
     
       5. A compound according to claim 1, which is methyl (1,4-dioxaspiro[4,5]decan-2-yl)methyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)pyridine-3,5-dicarboxylate. 
     
     
       6. A compound according to claim 1, which is methyl (2,2-diphenyl-1,3-dioxolan-4-yl)methyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)pyridine-3,5-dicarboxylate. 
     
     
       7. A pharmaceutical composition comprising, in association with physiologically acceptable excipient, an effective vasodilating amount of a compound selected from the group consisting of (1) 1,4-dihydro-2,6-dimethylphyidine-3,5-dicarboxylic acid esters of the formula I according to claim 1;   (ii) optical isomers thereof; and   (iii) diastereoisomers thereof.   
     
     
       8. A method of treatment of hypertension and cardiac insufficiency, which comprises administering to a human being an effective vasodilating amount of a compound selected form the group consisting of (i) 1,4-dihydro-2,6-dimethylpyridine-3,5-dicarboxylic acid esters of the formula of claim 1;   (ii) optical isomers thereof; and   (iii) diastereoisomers thereof.